The present invention relates to the field of derivatives of psoralen. It relates more particularly to monofunctional derivatives of psoralen, viz., pyrido (3', 4'; 4,5)furo(3,2-g) coumarins or pyrido(3,4-h) psoralens. The present invention is also concerned with a process of preparing such compounds. The invention also relates to the use of such compounds in cosmetology in particular for stimulating the pigmentation of the skin and as a medicinal for treating skin afflictions. The invention also relates to cosmetic compositions and pharmaceutical compositions having such compounds as their active ingredients.
Photochemical therapy which relies on the activation of photoactive molecules of the furocoumarin family, namely psoralens, on human skin by ultraviolet A radiation is rapidly developing in dermatology. It is indeed a particularly effective and convenient therapeutic technique for the treatment of mild chronic inflammatory dermatoses such as psoriasis which affects 2-3% of the world's population and for the treatment of malignant dermatoses such as mycosis fungoides, malignant cutaneous lymphoma, which is rare but has a particularly severe development. This therapeutic technique has been employed with a certain amount of success in the treatment of numerous chronic inflammatory skin diseases such as atypical eczema, lichen planus, parapsoriasis guttata, pruritis of the hemodialysed beings, in photodermatoses and in depigmentation diseases such as vitiligo.
By way of a reference illustrating the prior art French patent publication No. 2,405,067 may be cited, which concerns pharmaceutical compositions containing monofunctionals derivatives of psoralen for the treatment of skin afflictions. This patent publication, is incorporated by reference in the present specification.
Briefly, for the treatment of skin diseases such as psoriasis, certain furocoumarins or psoralens are administered in association with near ultraviolet light (UVA). This phototherapy is known as PUVA therapy.
The most recent studies have demonstrated that bifunctional psoralens such as 8-methoxy psoralen (abbreviated 8-MOP) and 5-methoxy psoralen (abbreviated 5-MOP) in the conditions of treatment, i.e., in the presence of near ultraviolet light (UVA) is carcinogenic in mice. On the contrary, 3-carbethoxy psoralen (abbreviated 3-CPs) is a monofunctional derivative of psoralen and is completely safe from this point of view. It has also been demonstrated that 3-CPs has a therapeutic activity for patients afflicted with psoriasis.
The psoralens currently used in therapy, such as 8-methoxypsoralen or 5-methoxypsoralen, are capable of forming cross-links in DNA, which cross-links are difficult to repair and capable of introducing errors in genetic replication. This property doubtless explains their high mutagenic activity and carcinogenesis in animals. They are therefore effective medicines but probably not devoid of risk for continual use on human beings. This is the reason photochemical therapy is prohibited for youths up to the age of 18-20 years and one tries to use it as little as possible before the age of 50.
In cosmetology, products are also known which stimulate pigmentation and are comprised of derivatives of psoralen such as 5-methoxy psoralen (or 5-MOP). They have applications in cosmetic compositions for tanning the skin and/or protecting skin against the sun. The drawback with such products is that they are mutagenic.